The long term objective of this project is the development of model systems elucidating the host/parasite interactions controlling the relationship between the nematode, Strongyloides stercoralis, and its usual hosts (man, primates, dogs). In this proposal, we introduce the use of a new model, the gerbil, in addition to the canine model that we have employed for several years. Specifically, we plan to examine mechanisms by which chronic and hyperinfections of S. stercoralis are maintained in the host. We propose: (1) In vivo studies testing the hypothesis that the long-persisting infections are maintained by episodic resumption of oviposition by senescent females, followed by an autoinfective replacement of the parthenogenetic maternal population by its progeny. (2) In vivo studies to elaborate and test the competing hypotheses that autoinfective development is (a) merely a reflection of increased opportunity to attain infectivity while the larva is still in the gut or (b) an obligate alternative mode of development programmed in the ovic juvenile. (3) In vivo studies to elaborate and test the competing hypotheses that the termination of an autoinfective burst is (a) determined by host mediated changes in the developmental pathway or (b) a density dependent change in developmental pathway. (4) In vitro studies of the role of amphidial neurons in controlling development. Amphidial neurons of culture-derived larvae will be ablated with a microlaser to determine which neuron(s) control the exit from developmental arrest which characterizes the infective larva. Amphidial neurons of host-derived larvae will be ablated to determine which neurons mediate the decision between direct and indirect development. Finally, we will attempt to determine whether these neurons control the decision for or against autoinfective development. As a basis for these studies we will continue 3D reconstruction of the sensory ultrastructure of relevant larval stages.